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Trial · Interventional

CompletedPhase 2Results postedRegistry data

A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer

NCTNCT00781911 (opens ClinicalTrials.gov in a new tab)Other id13929Other idCP13-0710Other idI5A-IE-JAEE

Overview

Status
Completed
Phase
Phase 2
Enrollment
43 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Not randomized · Open label (no masking)
Countries
1 country

United States

Start
Feb 2009
Primary completion
Jul 2011
Completion
May 2016
First posted
29 Oct 2008 (estimated)
Last update posted
20 Sept 2019
Conditions
Carcinoma · Neuroendocrine Tumors

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2010201220142016
  1. Ph 2

    A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer

    NCT00781911

    Feb 2009 to May 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Determine the 6-month progression free survival (PFS) rate associated with cixutumumab in combination with depot octreotide acetate (octreotide) in participants with metastatic neuroendocrine tumors.

Interventions

  • CixutumumabBiological
  • depot octreotideDrug

Arms2

  • Experimental

    Carcinoid tumor

    Participants with carcinoid tumor will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.

  • Experimental

    Islet cell carcinoma

    Participants with islet cell carcinoma will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months

    Time frame · From Start of Study Treatment to Progressive Disease or Death Due to Any Cause (Up to 6 Months)

    Registry description

    Percentage of participants who are alive and progression-free at 6 month from start of the study treatment over all participants. PFS is defined as the time from the start of study treatment until the date of objectively determined progressive disease (PD) or death due to any cause. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS was estimated by the binomial distribution and Kaplan-Meier method.

Secondary outcomes(10)
  1. Percentage of Participants Who Achieve Modified Objective Response Rate (ORR) of Complete Response (CR), Partial Response (PR) and Minor Response (MR) Modified Objective Response Rate (mORR)

    Time frame · From Start of Treatment Baseline to Disease Progression (Up to 18 Months)

    Registry description

    Modified ORR is defined as CR+ PR + MR. According to RECIST v1.0, CR was defined as the disappearance of all target and non-target lesions; PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD and MR defined as 20% - 29% reduction. Disease progression defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions.

  2. Percentage of Participants With a Biochemical Response Rate

    Time frame · From Start of Treatment Up to 18 Months

    Registry description

    Determine the biochemical response rate (≥ 50% reduction in tumor-specific markers; may include, not limited to 24 hour urine 5-hydroxyindoleacetic acid, chromogranin A, adrenocorticotropin hormone (ACTH), or gastrin) in the subset of participants with biochemically measurable disease.

  3. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

    Time frame · 18 months

    Registry description

    Number of participants that had at least one TEAE is presented. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

  4. Pharmacokinetics (PK): Maximum Concentration (Cmax) Cycle 1

    Time frame · Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

  5. PK: Half-life (t 1/2) Cycle 1

    Time frame · Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

  6. PK: Area Under Concentration (AUCinf) Cycle 1

    Time frame · Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

  7. PK: Clearance (CL) Cycle 1

    Time frame · Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

  8. PK: Volume at Steady State (Vss) Cycle 1

    Time frame · Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

  9. Serum Anti-Cixutumumab Antibody Assessment

    Time frame · 18 months

  10. Pharmacodynamics Markers; Concentration of Insulin-like Growth Factor I, II (IGF-I, IGF-II), IGF Body Fat (IGFBF)-1 and IGFBF-2

    Time frame · 18 months

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· From Start of Study Treatment to Progressive Disease or Death Due to Any Cause (Up to 6 Months)

Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months

GroupValue (percentage of participants)
Carcinoid Tumor45.2
Islet Cell Carcinoma41.7
Secondary and other outcome results(7)
Secondary outcomeNumber· From Start of Treatment Baseline to Disease Progression (Up to 18 Months)

Percentage of Participants Who Achieve Modified Objective Response Rate (ORR) of Complete Response (CR), Partial Response (PR) and Minor Response (MR) Modified Objective Response Rate (mORR)

GroupValue (percentage of participants)
Carcinoid Tumor3.2
Islet Cell Carcinoma0
Secondary outcomeNumber· From Start of Treatment Up to 18 Months

Percentage of Participants With a Biochemical Response Rate

GroupValue (percentage of participants)
Carcinoid Tumor0.0
Islet Cell Carcinoma22.2
Secondary outcomeCount of participants· 18 months

Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

GroupValue (Participants)
Carcinoid Tumor31
Islet Cell Carcinoma12
Secondary outcome· Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

Pharmacokinetics (PK): Maximum Concentration (Cmax) Cycle 1

GroupValue
Carcinoid Tumornot posted
Islet Cell Carcinomanot posted
Secondary outcome· Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

PK: Half-life (t 1/2) Cycle 1

GroupValue
Carcinoid Tumornot posted
Islet Cell Carcinomanot posted
Secondary outcome· Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

PK: Area Under Concentration (AUCinf) Cycle 1

GroupValue
Carcinoid Tumornot posted
Islet Cell Carcinomanot posted
Secondary outcome· Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

PK: Clearance (CL) Cycle 1

GroupValue
Carcinoid Tumornot posted
Islet Cell Carcinomanot posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Carcinoid TumorParticipants with carcinoid tumor received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide continued to receive the same dose and schedule of their last regimen.–12 / 3131 / 31
Islet Cell CarcinomaParticipants with islet cell carcinoma received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide continued to receive the same dose and schedule of their last regimen.–6 / 1212 / 12

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * The participant has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors * The participant has metastatic disease at the time of study entry * The participant must have a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, measurable by elevated tumor markers (eg, 24-hour urine 5-HIAA, chromogranin A, adrenocorticotropin hormone (ACTH), gastrin, or other tumor specific biochemical markers), or both * The participant is age ≥ 18 years * The participant's tumor has Ki-67 expression ≤ 20% * The participant is receiving depot octreotide therapy at the time of enrolling into the study * The participant has received 0 - 2 systemic anticancer regimens in addition to depot octreotide, which may have included chemotherapy, interferon, antiangiogenic therapy, other targeted treatments, or a combination of such treatments * The participant is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy * The participant has experienced radiographic, biochemical, and/or scintigraphic disease progression while on a regimen that includes octreotide * The participant has completed prior chemotherapy and/or radiotherapy with curative intent at least 3 weeks prior to the administration of the first dose of study therapy. Participants that have received palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible * The participant has a life expectancy of \> 3 months * The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 * The participant has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/microliters (μL), hemoglobin ≥ 9 gram/deciliter (g/dL), and platelet count ≥100,000/μL * The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases) * The participant either has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the ULN, or is on a stable dose of anticoagulant * The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliter/minute (mL/min) for participants with creatinine levels above the ULN * The participant has fasting serum glucose \< 160 milligram/deciliter (mg/dL) and hemoglobin A1c (HgbA1c)≤ 7. If baseline nonfasting glucose is \< 160 mg/dL, fasting glucose measurement is not required * Because the teratogenicity of cixutumumab is not known, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation * The participant has the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * The participant has uncontrolled brain or leptomeningeal metastases * The participant has not recovered to Grade ≤ 1 from adverse events due to agents administered more than 4 weeks prior to study entry (except for alopecia) * The participant is receiving any other investigational agent(s) * The participant has received therapeutic radiolabeled somatostatin analogues * The participant has received more than 2 prior regimens of systemic therapy in the metastatic setting * The participant has a history of treatment with other agents targeting the IGF receptor * The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of cixutumumab or to octreotide * The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their fasting glucose \< 160 mg/dL or below the ULN and that they are on a stable dietary or therapeutic regimen for this condition * The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * The participant is pregnant or lactating * The participant is known to be positive for infection with the human immunodeficiency virus * The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected or treated with no known active disease present and no treatment administered for the last 3 years

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